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Background and objective Small cell lung cancer (SCLC) is known as recalcitrant cancer with high malignancy and heterogeneity. Immunotherapy has changed the treatment pattern of extensive-disease SCLC (ED-SCLC), but the beneficiary population is limited. Therefore, exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC. SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase M1 (PKM1) is one of the isozymes of PK, an important rate-limiting enzyme in glycolysis pathway. Previous studies have shown that PKM1 is related to autophagy and drug sensitivity, however, how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear. The aim of this study was to investigate the biological functions of PKM1 in SCLC, including its effects on proliferation, migration, autophagy, drug sensitivity, and expression of neuroendocrine (NE)-related markers in SCLC. Methods Western blot was used to detect the expression level of PKM1 in SCLC cells. PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection. Proliferation of cells and drug sensitivity were detected by MTT, and migration ability of cells was determined by Transwell. The level of autophagy was detected by flow cytometry. Western blot was used to determine the expression levels of NE-related proteins. Results PKM1 was differentially expressed among various SCLC cell lines, and was lower in H1092 cells (P

Objective To prepare liposomes encapsulate hemoglobin and paclitaxel(LEHP)to improve tumor hypoxia resistance. Methods LEHP were prepared by thin-film method, and the particle size, Zeta potential and polydispersity were investigated by nanoparticle size analyzer, and encapsulation efficiency was investigated by high performance liquid chromatography, and the interaction between the liposomes and tumor cells was evaluated by in vitro cell experiments. Results The optimal preparation conditions of LEHP was as follows: total phospholipid 36 mM, DPPC∶Dope∶cholesterol molar ratio 7∶2∶1, paclitaxel 3 mg, hydrated with 3 mg·mL-1 Hb-PBS for 30 min at room temperature; The average particle size was (189.17±8.22) nm, polydispersity was 0.14±0.023, paclitaxel encapsulation efficiency was (58.27±2.55)%, hemoglobin content was (0.63±0.05) mg·mL-1. In vitro cell experiments, the killing effect of LEHP was about 1.5 times that of LEP, about 1.2 times that of LEP, and ROS production was about 1.8 times that of LEP. Conclusion The preparation conditions of LEHP was optimized, and cell experiments showed that LEHP can promote tumor cell apoptosis by improving hypoxia and increasing ROS production, which is expected to provide a safe and effective new method for drug resistance caused by tumor hypoxia.

Objective To prepare microneedles(MNs) loaded with platelet-rich plasma lysate (PL) using Carboxymethyl chitosan (CMCS), and explore the prospect of PL MNs in the treatment of diabetic wounds. Methods CMCS was used as the basic material, and an appropriate amount of polyvinylpyrrolidone (PVPK-60) was added to prepare needle materials of different concentrations, and the optimal concentration was determined by investigating the needle formation rate, morphological characteristics and mechanical properties, and the growth factor activity in PL MNs was investigated. The diabetic mice were randomly divided into four groups after the back wound was made, the control group did not do any treatment, the PL smear group was treated with PL smearing, the blank MNs group was treated with MNs without PL, and the PL MNs group was treated with PL microneedles. The effect of PL MNs in wound healing in diabetic mice was evaluated through body observation, H&E staining and immunohistochemistry results. Results When PVPK60 was 40 mg/mL, the needle formation rate was 100%, the array was complete, the needle body was full, and the needle was sharp. According to the results of mechanical-displacement curve and weight pressure change experiment, the prepared PL MNs have good mechanical strength. The results of growth factor analysis indicated that the content of vascular endothelial growth factor (VEGF) in PL was (625±35) pg/mL, and the content of platelet-derived growth factor-BB (PDGF-BB) was (18 741±1 287) pg/mL. After making the MNs, the VEGF content was (183±2) pg/mL, and the PDGF-BB content was (8049±1157) pg/mL. Although the concentration of growth factors decreased, growth factor activity was still preserved.The results of wound healing experiments in diabetic mice showed that the PL MNs group had better healing, and the wound healing rate was different from that of three groups (P

Red blood cells(RBCs), as the most abundant types of blood cells in the blood, have several advantages as a drug delivery system due to their ultra-long circulation half-life, good biocompatibility, and biodegradability. To date, a variety of RBCs-based drug delivery techniques have been developed for the treatment of infection diseases, cancers, chronic diseases, and autoimmune diseases. This review summarized the progress of RBCs related drug delivery systems, and discussed the advantages and disadvantages of different loading methods and their pre-clinical application progress, promoting the research and development of drug delivery.

Objective To investigate the application prospect of platelet-rich plasma lysate (PL) microneedles in the treatment of wound healing by optimizing the preparation process and evaluating the activity of platelet growth factor. Methods Firstly, hyaluronic acid (HA) was used as needle matrix material, and the concentration of HA was preliminarily determined by investigating the fluidity of HA solution, shape of needle, pressure change performance and puncture performance.Combined with the results of HA dissolution in PL, mechanical properties of PL microneedles and skin puncture, the preparation process of platelet-rich plasma lysis microneedles (PLMN) was optimized to investigate the growth factor activity of PLMN and evaluate the effect of PLMN on wound healing in rats. Results When the concentration of HA was 30 mg/mL, the solution had good fluidity.The HA microneedles could pierce three layers of sealing film, with the puncture rate at 70%, and the solution had good mechanical properties.When HA was dissolved in PL at a concentration of 30 mg/mL at 4℃, the solution had no crystallization and was with good fluidity.The prepared PLMN showed good needle shape and no bending under HD microscope and scanning electron microscope.In vitro transdermal simulation results showed that PLMN could penetrate 4 layers of sealing membrane, and the puncture rate of the first three layers was more than 85%.In vivo lysis experiment showed that PLMNs could be completely dissolved within 10 min after being inserted into the body.Forty minutes later, the micropores left after the insertion of the microneedle were almost closed, without redness, swelling, erythema and other adverse reactions.In vitro and in vivo transdermal experiments showed that clear blue holes were visible after PLMNs penetrated the skin stain, indicating that the microneedles could pierce the skin barrier.Growth factor detection results showed that the content of platelet-derived growth factor (PDGF-BB) and transforming growth factor (TGFβ1) in platelet lysate were (17.67±1.23) ng/mL and (105.95±2.16) ng/mL, respectively.After PLMNs were prepared and stored at room temperature for 1 week, the content of PDGF-BB(ng/mL) and TGFβ1(ng/mL) were 15.48±2.12 and 56.26±1.53, respectively.Compared with PL(vs 17.67±1.23 and 105.95±2.16), the content of PDGF-BB and TGFβ1 decreased, but still maintained the activity of growth factors.The results of wound healing experiment in rats showed that the wound healing rate (%) of PLMN group on the third day was significantly different from that of the control group(52.51±6.15 vs 33.31±3.60, P

Objective To investigate the quality changes of suspended red blood cells (SRBCs) prepared from the blood of Tibetan high Hb population, and explore the availability and safety of blood collected from Tibetan high Hb population. Methods The voluntary blood donors were grouped according to the Hb concentration at the initial screening: female blood donors from Tibet Autonomous Region (>3 500 m) with Hb≥190 g/L and male blood donors with Hb≥210 g/L were classified as plateau high hemoglobin group. A total of 13 male blood donors from Tibet Autonomous Region were recruited. And the female blood donors (n=13) with Hb(115~165) g/L and male blood donors (n=12) with Hb(120~185) g/L from Chengdu were classified as control group. Whole blood of 200 mL specification was centrifuged to remove the plasma, and MAP additive solution was added to prepare SRBCs, then SRBCs were divided into four aliquots (50 mL/bag and stored at 4℃. Parameters as blood routine, free Hb and hemolysis rate were measured aseptically at day 1, 14, 21, 35 of storage. And 10 mL SRBCs was used to extract membrane proteins for tyrosine phosphorylation detection of band 3 protein. Results The RBCs counts(×1012/L), hematocrit(%) and hemoglobin(g/L) of Tibetan high Hb group and control group were 6.76±0.95 vs 4.65±0.52, 63.3±6.8 vs 43.1±4.4 and 214.4±19.8 vs 143.2±16.9 (P

Tumor heterogeneity is one of the characteristics of malignant tumors, which can cause differences in tumor growth rate, invasion, migration, drug sensitivity and prognosis. Discoveries and development upon on tumor-driver genes and targeted therapy paved the way on dealing with cancer diagnosis and treatment. However, the existence of tumor heterogeneity makes malignant tumor more hardly to overcome. It is generally present and far more complicated during the process of cancer recurrence, development and evolution. Thus, it has becoming key areas in precision medicine regarding to designing optimal therapeutic approaches targeting the mechanisms and phenotypes of tumor heterogeneity, based on novel detecting techniques and new concepts and theory. This review summarized the current references on tumor heterogeneity, in order to better understand the function and mechanisms, and eventually manage tumor heterogeneity through various methods.

Objective To study the relationship between myofibril fragmentation index （MFI） of human skeletal muscle and postmortem interval （PMI）. Methods The protein concentrations of human right biceps brachii muscle and right quadriceps femoris muscle were obtained at different PMI, and detected at room temperature by biuret method. The MFI of skeletal muscle at 540 nm was measured by ultraviolet spectrophotometer. Regression analysis was performed with time of death as independent variable （x） and MFI as dependent variable （y）. Results In early PMI, the MFI of human skeletal muscle increased obviously according to the prolongation of PMI, and peaking by 12 h and then tended to steady. Within 12 h after death, the regression equations of right biceps brachii muscle and right quadriceps femoris muscle were y=32.660+3.227 x（r=0.987 9） and y=32.380+3.495 x（r=0.983 9）, respectively. Conclusion There’s high correlation between MFI and PMI. Combining with forensic practice, MFI can be used for the estimation of early PMI （especially in 12 h）.

Aiming at protecting the confidentiality of data for cloud storage users,a scheme that encrypt data in cloud service providers was presented.The scheme constructed a closed-box computing environment by virtual machine isolation technique,improved algorithm of RSA to change keys without having to produce large prime numbers,transfer data and keys through SSL and encrypted data in the closed computing environment before storing to the distributed file system.Closed-box computing environment can prevent attacks from cloud administrators and malicious applications in the operating system.It also can guard against data leakage effectively.The result of experiment shows that the confidentiality of data improved and the performance loss is decreased considering to other cloud storage scheme that encrypt data in cloud.

Antimony (Sb) has been widely used in products such as fire retardants, glass, rubber, paint, ceramics and semiconductors. It is found throughout igneous rocks but can be enriched in sedimentary rocks such as abysmal clays, shales and clastic rocks. Sb commonly occurs in magmatic sulfide deposits related to gabbroic rocks, sulfide deposits related to granitic rocks, clastic rocks and carbonate rocks hosted in stratified W-Sb-Hg deposits, and hydrothermal Pb-Zn deposits. The analytical method of high precision determination of Sb isotopes is now available. Samples are commonly digested with different types of acids, and Sb is separated and concentrated by cation exchange column combined with Thiol cotton fiber or both anion and cation exchange columns. Sb isotopes are determined by MC-ICP-MS coupled with hydride generation. The mass discrimination of equipment is commonly corrected by sample standard bracketing, using In and Sn internal standards. Different geological reservoirs have variable Sb isotope compositions (up to 18‱), with seawater of about 3.7‱, silicate rocks of 0.9‱ to 2.9‱, and sulfides (stibnite, sphalerite, pyrite, marcasite) of -1.9‱ to 16.9‱. Moreover, stibnites from different countries have different Sb isotope compositions. Glass from different places of production also shows different Sb isotope compositions. Sb isotopes will fractionate up to about 9‱ and 4‱ during oxide-reduction process (or sulfide precipitation) and inorganic absorption process, respectively. Therefore, Sb isotopes may serve as a geochemical tracer, which play an important role in indicating the source of ore-forming materials, portraying the ore-forming process and revealing the ore-forming mechanism. This isotope system can also be used to trace heavy metal pollution and can be used in archaeology.

Witnesses of a dynamic accumulator (DA) can ensure whether an object has been accumulated.On the basis of this,node membership in a cluster was verified and a novel authenticated group key management protocol was proposed,which supports node revocation and addition.In order to establish a group key for a cluster,each member provides their assigned number to join accumulation.DAAG can not only guarantee the confidentiality of witnesses,but also keep non-members from calculating novel group keys by binding witness with group key update.The security and performance analyses show that DAAG is resistant against replay attack,forgery attack and collusion attack,and can provide forward security and backward security.

The trust torque was defined as the product of trust gravitation and trust radius and the grid resource selection model based on trust torque was proposed.The grid resources are divided into many trusted resource domains according to different types and the grid resources of each domain are managed by its domain agent.A resource selection algorithm is realized by trust evaluation of resource nodes and comprehensive judgment of historical transaction experiences,current resource attributes and personal preferences.The algorithm not only pays attention to the service quality of resource selection for users,but also meets the requirements of different users.Simulation results verify the feasibility and effectiveness of our model.

Based on multi-sensor data fusion technology,a new intrusion detection data fusion model-IDSFP was pre-sented.The model was characterized by correlating and merging alerts of different types of IDS,generating the measures of the security situation,thus constituting the evidence.Current security situation of network was evaluated by applying the D-S evidence theory,and various IDS of network were adjusted dynamically to strengthen the detection of the data which relates to the attack attempt.Consequently,the false positive rate and the false negative rate are effectively reduced,and the detection efficiency of IDS is accordingly improved.

Taking the Tugeligaole sub-basin of the Jilantai Salt Lake Basin in Inner Mongolia as the typical study area, the groundwater samples of 22 points were collected, and their main characteristic indexes were tested during the wet season and the dry season separately in 2021. Mathematical statistics, Piper triangular diagrams, a Gibbs plot, ionic relations, and factor analysis were used to analyze and discuss the hydrochemical characteristics and formation mechanism of groundwater in different periods. Based on the evaluation of the groundwater quality using the water quality index(WQI) method, the potential risks of groundwater Cr 6+ and F - were evaluated using the health risk evaluation model. The results showed that the groundwater was overall weakly alkaline; the dominant anions and cations during the different periods were Cl - and Na + , and the water chemistry type was mainly Cl - -Na + ; the groundwater quality was generally good, and the difference in water quality between the wet season and the dry season was not significant; adults and children had higher carcinogenic health risks in the dry season than that in the wet season, and the health risks of children were significantly higher than those in adults. The maximum carcinogenic health risk of drinking water exposure to Cr 6+ in adults and children was higher than the maximum acceptable risk level(5×10 -5 ). The chemical evolution of groundwater was mainly affected by evaporative concentration, evaporative salt rock dissolution, and cation exchange, and the main control factors were evaporative concentration(contribution rate of 54.19%), native geological environment factors(contribution rate of 12.99%), and carbonate rock dissolution(contribution rate of 11.66%). The study results have significance to some degree to the sustainable exploitation and utilization of groundwater resources and environmental protection of the salt lake basin.

In this study, we collected precipitation from February 2020 to February 2022 and the surface water and groundwater in the wet (August) and dry (October) periods of 2021 in the Shandian River Basin. Stable isotope technology was used to analyze the temporal and spatial changes in the hydrogen and oxygen stable isotopes of the "three waters" in the basin to explore the relationship between water isomorphs and environmental factors and to reveal the water conversion relationship using the end element mixing model. The results showed that the slope and intercept of the local precipitation line were smaller than the local atmospheric precipitation line. The water vapor mainly came from westerly water vapor, polar air mass, and East Asian monsoon circulation. The precipitation isotope had a significant temperature effect. In terms of time, the isotopes of surface water and groundwater were more enriched in the dry season than those in the wet season, and the d -excess values of surface water and groundwater were lower than the global average, indicating strong local evaporation. Spatially, the δ 18 O value of the rivers had the same change characteristics in the wet and dry seasons, showing gradual enrichment from the upstream to the downstream, and the groundwater δ 18 O high value area was unevenly distributed in space, with groundwater δ 18 O values becoming more depleted with the increase in burial depth. The highest slope of the groundwater water line was 7.87 in the wet season, which was very close to the slope of the local atmospheric precipitation line and river water line, indicating that there was a complex hydraulic connection between the "three waters" in the wet season. The surface water in the study area was mainly supplied by precipitation during the wet season and then by groundwater runoff. These results can provide a theoretical basis for revealing the hydrological cycle in arid and semi-arid areas.

We examined the characteristics of water use in typical tree species of arbor and shrub in Hunshandake Sandy Land, Populus cathayana and Salix gordejevii , in the different seasons, with the aim to provide theoretical basis for the structural optimization of the artificial shelterbelt. Samples of precipitation, soil water, groundwater and stem water of the two vegetation were collected, and their distribution characteristics of δD-δ 18 O were analyzed by hydrogen and oxygen stable isotope technology. The contribution rate of these potential water source to the arbor and shrub species were calculated using multi-source linear mixing model. The precipitation equation line in the study area was δ D =7.84δ 18 O +9.12, while soil moisture lines in the dry and wet season were δ D =3.56δ 18 O -41.28 and δ D =4.30δ 18 O -42.02, respectively. The δD-δ 18 O of soil water and stem water in the two seasons were lower than the precipitation δD-δ 18 O, indicating that both of them were strongly affected by the evaporation. Soil water contents in the shallow layer were strongly affected by rainfall and evaporation, with substantial fluctuation. With the increases of soil depth, soil water content tended to be stable, and the hydrogen and oxygen isotope in each soil layer showed significant differences. In the dry season, P. cathayana mainly utilized soil water in 0-40 cm and 120-200 cm layers, with contribution rates of 50.2% and 31.5%, respectively. S. gordejevii mainly absorbed soil water in 20-40 cm and 60-100 cm layers, and the contribution rates were 53.2% and 22.9%, respectively. In the wet season, the greatest contribution of soil water to P. cathayana was mainly in the 0-40 cm soil layer, accounting for 72.8%. S. gordejevii was mainly in the 0-20 cm soil water, evenly utilized the deeper soil water and groundwater. Due to the differences in root depth and distribution of the arbor and shrub, their water use strategies differed in different seasons, which was conducive to the stability of the shelterbelt community and tree species coexistence in Hunshandake Sandy Land. We proposed that the mixed planting species with different root depth should be considered in the future planting of artificial shelterbelt, which would help rationally utilize water resources and maintain the stability of sandy land ecosystem.

Most quantitative models used in laser-induced breakdown spectroscopy (LIBS) are based on the hypothesis that laser-induced plasma approaches the state of local thermal equilibrium (LTE). However, the local equilibrium is possible only at a specific time segment during the evolution. As the populations of each energy level does not follow Boltzmann distribution in non-LTE condition, those quantitative models using single spectral line would be inaccurate. A multivariate nonlinear model, in which the LTE is not required, was proposed in this article to reduce the signal fluctuation and improve the accuracy of quantitative analysis. This multivariate nonlinear model was compared with the internal calibration model which is based on the LTE condition. The content of Mn in steel samples was determined by using the two models, respectively. A minor error and a minor relative standard deviation (RSD) were observed in multivariate nonlinear model. This result demonstrates that multivariate nonlinear model can improve measurement accuracy and repeatability.

Objective: To analyze the impact of diabetes mellitus on the clinicopathological factors and prognosis of patients with colorectal cancer., Methods: A total of 599 patients with colorectal cancer treated between January 2000 and June 2007 were collected retrospectively. The patients were divided into diabetes mellitus (DM) group and non-diabetes mellitus (NDM) group. The pathologic factors data was compared between the two groups, and the Logistic multivariable analysis was performed. The Cox regression model analysis of prognosis data was applied in 402 patients who underwent radical surgery without preoperative neoadjuvant therapy., Results: A total of 58 cases (9.7%) developed diabetes mellitus. Significant differences was found in the body-weight, age, hypertension between the two groups (P < 0.05), while no significant differences in the pathologic factors, such as tumor differentiation, invasion depth, lymph node involvement, TNM stage and lymphovascular invasion was found between the two groups (P > 0.05). There was no significant correlation between diabetes mellitus and the pathologic factors on the Logistic analysis (P > 0.05). Among the patients underwent radical surgery directly, neither disease progression curve (P = 0.521) nor overall survival curve (P = 0.909) presented significant differences between the two groups. It's not shown that diabetes mellitus was significantly associated with the prognosis of patients with colorectal cancer by using Cox regression analysis (P = 0.991)., Conclusions: Diabetes mellitus does not significantly influence the clinicopathological factors and the prognosis of colorectal cancer in patients receiving radical surgery, and it requires more investigation.

Objective: To examine the distributions of beta-catenin and adenomatous polyposis coli (APC) protein in the tooth germ, and obtain the messages of function of the two factors and the relationship between them., Methods: Mice were selected and cohabited with the ratio of female mice to male ones being 2:1, and Embryo day 0.5 was confirmed based on the finding of vaginal plug. The distributions of beta-catenin and APC protein in the Embryos on day 13.5, 14.5, 15.5, 16.5, 17.5 were examined in the paraffin-embedded sections by immunohistochemistry methods., Results: During E13.5 d to E17.5 d, positive expression of beta-catenin was found in the oral epithelium and the dental lamina, and became more and more strong. The staining were whole cell. During the bud stage, strong positive expression of APC protein was found in the oral epithelium and the dental lamina, but the expression displayed a down-regulation tendency. The staining was the cytomembrane and cytoplasm. There was negative correlation between beta-catenin and APC protein (P<0.01)., Conclusion: The result of beta-catenin suggests its contribution in the early development of enamel organ and the proliferation of cell. Coincidance of the two factors staining site was found, according to the statistics.

In the present paper, based on the exponential attenuation of atmospheric aerosol concentration with height, so using continuous spectrum sun-photometer, forward scatter visibility sensor and hygrothermograph, the authors measured the atmosphere column optical characteristic and plane spectral extinction coefficient on earth on the base of two experiments at some edge of ocean at the same time, respectively, set up the calculative method of multi-wavelength spectral aerosol scale height. Firstly, the authors obtained atmospheric horizontal extinction coefficient with forward scattering visibility sensor, which subtracted molecular extinction coefficient, and could get aerosol extinction coefficient near ground; Then, selecting sea salt model, using OPAC software, the authors also could calculate the aerosol extinction coefficient under different humidity (0%, 50%, 70%, 80%, 90%, 95%, 98% and 99%) and different wavelength (400, 450, 500, 550, 600, 650, 700 and 750 nm), the aerosol extinction coefficient was detected by visibility sensor, using interpolation method, respectively; Finally, using the data of atmospheric columniation optical thickness detected by continuous spectral sun-photometer and subtracted molecular optical thickness corresponding wavelengths were accounted out by Modtran 4. 0. The authors obtained the characteristic of spectral aerosol scale height of visible light (wavelength is 400, 440, 532, 550 and 690 nm): with wavelength increments, and spectral aerosol scale height was found to decline neither in inland nor in inshore in China; Spectral aerosol scale height in winter is higher than in summer in southeast inshore; but spectral aerosol scale height in winter is smaller in summer than in inland.

Objective: To compare the long-term efficacy of procedure for prolapse and hemorrhoids (PPH) and Milligan-Morgan hemorrhoidectomy (MMH) in the treatment of III and IV degree internal hemorrhoids., Methods: One hundred patients were randomly divided into two groups and received PPH (n=42) and MMH (n=58) respectively. After two years, the efficacy, complications and function of defecation were compared., Results: Two years after operation, the morbidities of hydrorrhea (2.38% vs 20.69%, P=0.007), dermal neoplasm formation (9.52% vs 25.86%, P=0.040) and narrowing in the caliber of the stools (2.38% vs 18.97%, P=0.027) were significantly lower in PPH group than those in MMH group (P<0.05). The morbidities of overall complication (9.52% vs 25.86%, P=0.040) and overall abnormal function of defecation (9.52% vs 29.31%, P=0.017) were lower in PPH group than those in MMH group (P<0.05). However, there were no significant differences of the morbidity of relapse (14.29% vs 10.34%, P=0.549), patient satisfactory degree (92.86% vs 87.93%, P=0.636) and overall symptom recurrence rate (19.05% vs 25.86%, P=0.424) between the two groups., Conclusions: Long-term efficacies of procedure for prolapse and hemorrhoids and Milligan-Morgan haemorrhoidectomy in the treatment of III and IV degree internal hemorrhoids are similar. PPH has better safety, less complications and less effect on abnormal function of defecation compared with MMH.